Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA175384 | ENA |
REPOSITORIES: ENA
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Project description:Surgical glaucoma therapy is characterized by implantation of an aqueous shunt either draining into the extraocular Tenon’s space or the intraocular suprachoroidal space. In both cases the long term drainage is hampered by fibrotic reactions around the outflow region of the shunt. The prevention of fibrosis should extend the operating life of the shunt. For an aqueous shunt draining from the anterior chamber into the choroidal space fibroblasts from the choroidea and/or the sclera are most likely responsible for a fibrotic response around the outflow region of such a shunt. A detailed characterization of fibroblasts derived from choroidea and sclera should provide information whether a fibrosis reaction can be inhibited by cell type specific agents. Therefore, we have decided to generate mRNA profiles of fibroblasts from the choroidea, sclera and Tenon’s space in order to look for potential pharmacological targets for fibrosis prevention. The three fibroblast types investigated share fibroblast specific gene expression patterns, concerning extracellular matrix proteins as collagens and fibronectin, but also show distinct mRNA patterns, which we plan to search for targets responsible for fibrotic processes which hopefully can be targeted by specific antifibrotic drugs.
2012-09-25 | GSE40929 | GEO
Project description:Surgical glaucoma therapy is characterized by implantation of an aqueous shunt either draining into the extraocular Tenon’s space or the intraocular suprachoroidal space. In both cases the long term drainage is hampered by fibrotic reactions around the outflow region of the shunt. The prevention of fibrosis should extend the operating life of the shunt. For an aqueous shunt draining from the anterior chamber into the choroidal space fibroblasts from the choroidea and/or the sclera are most likely responsible for a fibrotic response around the outflow region of such a shunt. A detailed characterization of fibroblasts derived from choroidea and sclera should provide information whether a fibrosis reaction can be inhibited by cell type specific agents. Therefore, we have decided to generate mRNA profiles of fibroblasts from the choroidea, sclera and Tenon’s space in order to look for potential pharmacological targets for fibrosis prevention. The three fibroblast types investigated share fibroblast specific gene expression patterns, concerning extracellular matrix proteins as collagens and fibronectin, but also show distinct mRNA patterns, which we plan to search for targets responsible for fibrotic processes which hopefully can be targeted by specific antifibrotic drugs. Three human fibroblast cell type cultures from different ocular tissues were established: sclera fibroblasts (hSF), choroidea fibroblasts (hCF), and Tenon’s space fibroblasts (hTF). For the gene expression analysis n = 5 for hCF, n = 4 for hSF, and n = 5 for hTF donor cells were cultivated from different donors. After appropriate cultivation, cells were harvested, RNA was extracted, purified and quantity and quality was assessed. All total RNA samples were analyzed by Affymetrix' Whole-Transcript Expression Analysis & Profiling Human Gene ST Arrays, respectively. In this set-up, we run = 5 arrays for hCF, n = 4 arrays for hSF, and n = 5 arrays for hTF i.e. one array per biological replicate. No technical replication was carried out. Microarray data analysis was carried out by using the Rosetta Resolver® system for gene expression data analysis (Rosetta Biosoftware, Seattle, WA, USA). In brief, the raw signals of the probes were summarized using RMA thereby generating probe set specific signal intensities. Chips were normalized by using quantile normalization. To compare RNA expression levels of genes in hCF, hSF and hTF, normalized expression signals of genes from corresponding samples were averaged and fold changes were calculated. To assess differences in mean signal intensities between experimental groups, ANOVA (analysis of variance, with Benjamini Hochberg test correction) and a post-hoc Scheffe test was performed. Rosetta Resolver ratio built statistics to correct for possible signal intensity bias were also considered. Only genes (1) an absolute fold change of ≥ 1.5 together with a Scheffe test p value ≤ 0.05 in at least one of the three pairwise comparisons hCF vs. hTF, hSF vs. hTF and hCF vs. hSF, resp., as well as (2) a ratio built p value ≤ 0.05 were deemed differentially expressed genes (DEG) and considered for further evaluation.
2012-09-25 | E-GEOD-40929 | biostudies-arrayexpress
Project description:Trabecular meshwork cells in eyes with glaucoma aquire mesenchymal phenotypes. The types of microRNAs in exosomes may differ between static and glaucomatous status and their effects on aqueous humor regulation are still uknown. We used microarrays to identify the differential microRNA expression related to interaction between trabecular meshwork cells and Schlemm's canal endothelial cells.
2021-11-17 | GSE175464 | GEO
Project description:Aqueous humor (AH) is the fluid in the anterior and posterior chambers of the eye that contains proteins regulating ocular homeostasis. Analysis of aqueous humor proteome is challenging mainly due to low sample volume and protein concentration. In this study, by utilizing state of the art technology, we performed Liquid-Chromatography Mass spectrometry (LC-MS/MS) analysis of 88 aqueous humor samples from subjects undergoing cataract surgery.
2021-09-09 | PXD022463 | Pride
Project description:PURPOSE: To investigate the circulatory microRNA (miRNA) profiles of aqueous, vitreous, and plasma in order to identify biomarkers in aqueous humor or plasma that are reflecting changes in vitreous of patients with diabetes. METHODS: Aqueous, vitreous and plasma samples were collected from a total of 27 patients - 11 controls (macular pucker or macular hole patients) and 16 patients with diabetes mellitus (DM) undergoing vitreoretinal surgery: DM-Type I with proliferative diabetic retinopathy (PDR) (DMI-PDR), DM Type II with PDR (DMII-PDR) and DM Type II with nonproliferative DR (DMII-NPDR). MiRNAs were isolated using Qiagen microRNeasy kit, quantified on BioAnalyzer, labeled with FlashTag kit, and profiled on Affymetrix GeneChip miRNA 3.0 microarrays. Data analysis was done using Expression Console (EC), Transcriptome Analysis Console (TAC), and Ingenuity Pathway Analysis (IPA) software. RESULTS: Our comparison of circulatory miRNA population of aqueous and vitreous humor and plasma showed that out of total of 847 human miRNA probes on the Affymetrix GeneChip miRNA 3.0 we found common miRNAs for both aqueous and vitreous samples, as well as larger number of unique miRNA, dependent on the DM type and presence of retinopathy. Most of the dysregulated miRNAs in aqueous and vitreous of DM patients were upregulated, while in plasma, most of the DM-specific miRNAs were downregulated. Dysregulation of miRNAs in aqueous generally do not appear to be a good representative of the miRNA abundance in vitreous, or plasma, although we did identify a few candidates for common biomarkers: let-7b, miR-320b, miR-762 and miR-4488. Additionally, each of the DR subtypes showed a set of miRNA that is uniquely dysregulated in each fluid, for example in aqueous samples for DMII-NPDR it was miR-455-3p, for DMII-PDR was miR-296, and for DMI-PDR it was miR-3202. Pathway analysis identified TGF-beta and VEGF pathways as the common targets for miRNAs dysregulated in DR aqueous and vitreous. CONCLUSIONS: The comparative profiling of circulatory miRNAs in aqueous, vitreous, and plasma showed that a small number of circulatory miRNAs displayed differential presence in controls vs. diabetic retinopathy. A pattern is emerging of sets of miRNA that are common or uniquely dysregulated in the blood plasma or ocular fluids of DR subtypes, offering promise for the use of ocular fluids and plasma for identifying diagnostic and therapeutic targets.
2020-06-27 | GSE140959 | GEO
Project description:In humans, the lacrimal gland produces the aqueous component of the tear film, which e.g. moistens and nourishes the ocular surface to maintain ophthalmic health. Decreased production of the aqueous component leads to the development of dry eye disease, which affects over 250 million people worldwide. Despite the impact on patients, the availability of primary human material to study underlying disease mechanisms is severely constrained. Here, we report the development of an immortalized human lacrimal gland epithelial cell line that improves accessibility to study the molecular pathogenesis-mechanisms of dry eye disease and link them to causal treatments.
2024-04-17 | GSE239464 | GEO
Project description:Molecular biomarkers for neurodegenerative diseases are critical for advancing diagnosis and therapy. Normal pressure hydrocephalus (NPH) is a neurological disorder characterized by progressive neurodegeneration, gait impairment, urinary incontinence and cognitive decline. In contrast to most other neurodegenerative disorders, NPH symptoms can be improved by the placement of a ventricular shunt that drains excess CSF. A major challenge in NPH management is the identification of patients who benefit from shunt surgery. Here, we perform genome-wide RNA sequencing of extracellular vesicles in CSF of 42 NPH patients, and we identify genes and pathways whose expression levels correlate with gait, urinary or cognitive symptom improvement after shunt surgery. We describe a machine learning algorithm trained on these gene expression profiles to predict shunt surgery response with high accuracy. The transcriptomic signatures we identified may have important implications for improving NPH diagnosis and treatment and for understanding disease aetiology.
2023-06-02 | GSE212236 | GEO
Project description:GPR158 Activates Cellular Stress Responses in Trabecular Meshwork Cells of the Eye’s Aqueous Outflow Pathways: Implications for Ocular Hypertension
| PRJNA988435 | ENA
Project description:Idiopathic Pulmonary Fibrosis (IPF) is characterized by progressive, often fatal loss of lung function due to overactive collagen production and tissue scarring. IPF patients have a sevenfold-increased risk of developing lung cancer. The COVID-19 pandemic has increased the number of patients with lung diseases, and infection can worsen prognoses for those with chronic lung diseases and disease-associated cancer. Understanding the molecular pathogenesis of IPFassociated lung cancer is imperative for identifying diagnostic biomarkers and targeted therapies that will facilitate prevention of IPF and progression to lung cancer. To understand how IPF-associated fibroblast activation, matrix remodeling, epithelial-mesenchymal transition, and immune modulation influences lung cancer predisposition, we developed a mouse model to recapitulate the molecular pathogenesis of pulmonary fibrosis-associated lung cancer using the bleomycin and Lewis Lung Carcinoma models. We demonstrate that development of pulmonary fibrosis-associated lung cancer is likely linked to increased abundance of tumor-associated macrophages and a unique gene signature that supports an immune-suppressive microenvironment through secreted factors. Not surprisingly, pre-existing fibrosis provides a pre-metastatic niche and results in augmented tumor growth, and tumors associated with bleomycin-induced fibrosis are characterized by a dramatic loss of cytokeratin expression, indicative of epithelial-to-mesenchymal transition. Implications: This characterization of tumors associated with lung diseases provides new therapeutic targets that may aid in the development of treatment paradigms for lung cancer patients with pre-existing pulmonary diseases.
2023-06-20 | GSE224134 | GEO
Project description:A high percentage of vision loss and blindness worldwide are due to glaucoma and cataracts ocular diseases. Small extracellular vesicles (sEVs) are small lipidic vesicles involved in transport and cell-to-cell communication, released into different body fluids including eye’s aqueous humor. The identification and characterization of the protein content of small extracellular vesicles in ocular pathologies has not been well elucidated yet. To that end, a by quantitative proteomics approach using Tandem Mass Tag (TMT) 10-Plex was performed to analyze the protein content of extracellular vesicles from patients´ aqueous humors with cataracts and glaucoma compared to healthy individuals (ICL). Labeled peptides were analyzed on an Orbitrap Exploris 480 equipped with FAIMS Pro Duo interface. Then, western blot (WB) and ELISA analyses using aqueous humor samples from ICL, cataracts, and glaucoma patients were performed for validation. From the TMT 10-plex analysis of sEVs, a total of 828 peptides and 192 proteins were identified and quantified. After data analysis with R program, 14 significantly dysregulated proteins from sEVs of aqueous humor in cataracts and 11 in glaucoma showed a fold change ≥1.5. Then, the dysregulation of 10 candidate dysregulated proteins was confirmed by WB and ELISA using directly aqueous humor samples. In addition, GAS6 and SPP1 were found to possess a high diagnostic ability of glaucoma patients. In conclusion, the proteomics analysis of sEVs from aqueous humor samples allowed the identification of GAS6 and SPP1 as glaucoma biomarkers, which in combination allowed for discriminating glaucoma patients from control individuals with an area under the curve (AUC) of 76.1%, and a sensitivity of 65.6%, and a specificity of 87.7%.
2024-11-04 | PXD048815 | Pride